1. Field of the Invention
This invention relates to filling sample chambers with liquid samples and/or reagents, and, more particularly, to a system for separately filling sample chambers provided in microcard substrates having at least two groups of sample chambers, each group having a network of passageways to connect the sample chambers therein with a group fill port.
2. Description of the Related Art
In the biological testing field, such methods as polymerase chain reaction (PCR), ligase chain reaction, oligonucleotide ligation assay, or hybridization assay are used to detect a reaction of a test sample to an analyte-specific reagent in each a plurality of small detection chambers sometimes referred to in the art as “spots.” Typically, an analyte-specific reagent is placed in each detection chamber in advance of conducting the testing method. These analyte-specific reagents in the detection chambers may be adapted to detect a wide variety of analyte classes in the liquid sample, including polynucleotides, polypeptides, polysaccharides, and small molecule analytes, by way of example only. One method of polynucleotide detection is the nuclease process referred to as “TaqMan”® (Roche Molecular Systems, Inc.), conducted during PCR. The above detection methods are well known in the art. They are described in detail in the following articles and patents: U.S. Pat. No. 5,210,015 of Gelfand et al.; U.S. Pat. No. 5,538,848 of Livak et al.; WO 91/17239 of Barany et al. published on Nov. 14, 1991; “A Ligase-Mediated Gene Detection Technique” by Landegren et al published in Science 241:1077-90 (1988); “High-density multiplex detection of nucleic acid sequences: oligonucleotide ligation assay and sequence-coded separation” by Grossman et al., published in Nucleic Acid Research 22:4527-34 (1994); and “Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay” by Nickerson et al., published in Proc. Natl. Acad. Sci. USA 87:8923-27 (1990).
While the biological testing science has achieved a highly sophisticated state of development, the mechanisms required for the practice of the above-mentioned testing methods efficiently and accurately are of relatively recent vintage. For example, a substrate for simultaneously testing a large number of analytes, which has a small sample size and a large number of detection chambers, has been described in published PCT International Application, WO 97/36681, assigned to the assignee of the present application, the disclosure of which is incorporated herein by reference.
Also, in a commonly assigned and published PCT International Application, WO 01/28684, the complete disclosure of which is incorporated by reference, a further development of a card-like substrate having a plurality of sample detection chambers is disclosed together with a system for filling the substrate with a liquid sample to react with reagents located in the sample detection chambers during thermal cycling of a PCR process. Such card-like substrates are a spatial variant of the micro-titer plate and are sometimes referred to as “microcards.” They typically contain 96, 384, or more, individual sample chambers, each having a volume of about 1.0 μL or less in a card size of 7 cm×11 cm×0.2 cm, for example.
The system for filling substrates disclosed in WO 01/28684 with liquid samples involves first evacuating the sample chambers and network of passageways connecting them with a fill port, and then allowing the liquid to flow into the fill port essentially under the differential in pressure between the evacuated chambers and passageways and atmospheric pressure. In so filling the sample chambers with a liquid sample, for example, it is desirable that gaseous components contained in the liquid be prevented from passing into the substrate, particularly as bubbles that result in a less than complete filling of the substrate with liquid. The filling system disclosed in WO 01/28684 includes a “priming” arrangement to minimize the presence of gas entering the substrate.